Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema (TRIOZ)

• ClinicalTrials.gov Identifier: NCT02556424
• Recruitment Status: Recruiting
• First Posted: September 22, 2015
• Last Update Posted: January 30, 2020
• Sponsor: Nantes University Hospital
• Information provided by (Responsible Party): Nantes University Hospital

Tracking Information

• First Submitted Date: May 29, 2015
• First Posted Date: September 22, 2015
• Last Update Posted Date: January 30, 2020
• Actual Study Start Date: January 2016
• Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2015)

Evaluation of the effectiveness of a subconjunctival injection of triamcinolone on reducing the central macular thickness versus an intravitreal implant of dexamethasone between patient selection and 2 months after treatment [ Time Frame: At 2 months after treatment ]

Difference of the central macular thickness in the treated eye, measured by Optical Coherence Tomography (OCT) spectral domain, for each patient between patient selection and 2 months after treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 19, 2016)

• Evaluation of the experience of the injection by a questionnaire (tolerable, unpleasant and very unpleasant) and by EVA (0 cm = no pain to 10 cm = extreme pain) [ Time Frame: At day 0 (= the day of the treatment) ]
  Scale of "patient experience" the day of the injection (tolerable, unpleasant, very unpleasant) and visual analogue scale (VAS)
• Evaluation of the effectiveness of the studied injection at each visit regarding gain in visual acuity (ETDRS) [ Time Frame: Up to 6 months ]
  Visual acuity (ETDRS)
• Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the anterior flare [ Time Frame: Up to 6 months ]
  Anterior flare ("Lampe A Fente" and Laser Flare Meter, if available)
• Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the vitreous haze [ Time Frame: Up to 6 months ]
  Vitreous flare
• Evaluation of the effectiveness of the studied injection at each visit regarding central macular thickness measured by OCT, allowing the evaluation of the duration of action of the treatment [ Time Frame: Up to 6 months ]
  Central macular thickness of the eye treated for determining the duration of action
• Evaluation of the effectiveness of the studied injection at each visit regarding local and general tolerance, by collecting all Adverse Events (AEs) / Serious Adverse Events (SAEs) [ Time Frame: Up to 6 months ]
  Evaluation of tolerance by collecting all AEs / SAEs of randomized patients, such as intra-ocular hypertension, cataracts, endophthalmitis, poor glycemic and/or blood pressure control
• Evaluation of the effectiveness of the studied injection at each visit regarding patients' quality of life [ Time Frame: Up to 6 months ]
  Patients' quality of life questionnaire (EQ-5D)

Original Secondary Outcome Measures (submitted: September 18, 2015)

• Evaluation of the experience of the injection by a questionnaire (tolerable, unpleasant and very unpleasant) and by EVA (0 cm = no pain to 10 cm = extreme pain) [ Time Frame: At day 0 (= the day of the treatment) ]
  Scale of "patient experience" the day of the injection (tolerable, unpleasant, very unpleasant) and visual analogue scale (VAS)
• Evaluation of the effectiveness of the studied injection at each visit regarding gain in visual acuity (ETDRS) [ Time Frame: Up to 6 months ]
  Visual acuity (ETDRS) Visual acuity (ETDRS)
• Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the anterior flare [ Time Frame: Up to 6 months ]
  Anterior flare ("Lampe A Fente" and Laser Flare Meter, if available)
• Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the vitreous haze [ Time Frame: Up to 6 months ]
  Vitreous flare
• Evaluation of the effectiveness of the studied injection at each visit regarding central macular thickness measured by OCT, allowing the evaluation of the duration of action of the treatment [ Time Frame: Up to 6 months ]
  Central macular thickness of the eye treated for determining the duration of action
• Evaluation of the effectiveness of the studied injection at each visit regarding local and general tolerance, by collecting all Adverse Events (AEs) / Serious Adverse Events (SAEs) [ Time Frame: Up to 6 months ]
  Evaluation of tolerance by collecting all AEs / SAEs of randomized patients, such as intra-ocular hypertension, cataracts, endophthalmitis, poor glycemic and/or blood pressure control
• Evaluation of the effectiveness of the studied injection at each visit regarding patients' quality of life [ Time Frame: Up to 6 months ]
  Patients' quality of life questionnaire (EQ-5D)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema
• Official Title: Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema

Brief Summary

Corticosteroids, whether injected peri- or intra-ocularly, remain indispensable tools of the therapeutic arsenal in treating inflammatory macular edema. However, a few years ago, only triamcinolone acetonide was available to ophthalmologists. This molecule, developed initially for rheumatological or dermatological use, has been increasingly deployed in ophthalmology, while still off-label.

In 2011, the delivery system of dexamethasone from biodegradable and injectable implant into the vitreous cavity obtained the label for inflammatory macular edema. This protocol is therefore designed to compare the efficacy and safety of peri- and intra-ocular injections of corticosteroids in the treatment of inflammatory macular edema.

• Detailed Description: This research compares the implantation techniques of corticosteroids in the eye, with two groups of equal size being followed. This is a multi-center, controlled study, with the reference drug being the intravitreal implant of 700μg of dexamethasone (Ozurdex®) compared to subconjunctival injection of triamcinolone (Kénacort retard®). This is an open, prospective, randomized study. It is not possible, for technical reasons, to inject blind two products with different injection routes and that are visible to the investigator during control examinations (sub-conjunctival crystals and intravitreal implant). However, the assessment of visual acuity and central macular thickness will be performed by an uninformed ophthalmologist.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Inflammatory Macular Edema

Intervention

• Drug: Dexamethasone
  Intravitreal implant at D0
  Other Name: Ozurdex®
• Drug: Triamcinolone
  Subconjunctival injection at 4 mm from the limbus at 6 o'clock
  Other Name: Kénacort retard®

Study Arms

• Active Comparator: Reference Drug
  Intravitreal implant of 700μg of dexamethasone (Ozurdex®)
  Intervention: Drug: Dexamethasone
• Experimental: Tested Drug
  Subconjunctival injection of 16 mg triamcinolone (Kénacort Retard®)
  Intervention: Drug: Triamcinolone

• Publications *: Couret C, Poinas A, Volteau C, Riche VP, Le Lez ML, Errera MH, Creuzot-Garcher C, Baillif S, Kodjikian L, Ivan C, Le Jumeau de Kergaradec LM, Chiffoleau A, Jobert A, Jaulin J, Biron L, Hervouet E, Weber M. Comparison of two techniques used in routine care for the treatment of inflammatory macular oedema, subconjunctival triamcinolone injection and intravitreal dexamethasone implant: medical and economic importance of this randomized controlled trial. Trials. 2020 Feb 10;21(1):159. doi: 10.1186/s13063-020-4066-0.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 18, 2015): 142
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2021
• Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient, male or female (under effective contraception if premenopausal) over 18 years old
• Patient affiliated with a social security plan
• Patient able to understand and follow the instructions of the study
• Patient having signed an informed consent
• Patient having a central macular thickness greater than 320μm (Spectral Domain, 270µm Time Domain)
• Patient with an inflammatory macular edema, unilateral or bilateral (in the case of a bilateral inflammatory macular edema, the eye most affected will be treated)

Exclusion Criteria:

• Patient with an infectious uveitis
• Patient with uncontrolled active infection
• Patient receiving an unbalanced general anti-inflammatory and/or immunosuppressive and/or immunomodulatory therapy (recent modification <1 month)
• Patient having a history of glaucoma and/or ocular hypertension in the eye studied (intraocular pressure (IOP) > 25 mmHg without antiglaucoma medication or > 21 mmHg with antiglaucoma combination therapy) and/or cortisone-causing-hypertension not controlled by an antiglaucoma dual therapy
• Patient with uncontrolled diabetes (HbA1c> 8%) or unbalanced hypertension (Systolic Blood Pressure > 160 mmHg and/or Diastolic Blood Pressure > 100mmHg)
• Edematous diabetic maculopathy
• Patient who had received triamcinolone (subconjunctivally or sub-tenon) 3 months before randomization, or 700μg dexamethasone intravitreally 6 months before randomization
• Suspected or active ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, such as active epithelial keratitis with herpes simplex (dendritic keratitis), vaccinia, varicella, mycobacterial infections and mycoses
• History of ocular herpes infection or central serous chorioretinopathy
• Aphakic eye with rupture of the posterior lens capsule
• Eye with implant in the anterior chamber, iris- or transscleral-fixated intraocular implant and rupture of the posterior lens capsule
• Uncontrolled systemic inflammatory disease.
• Known hypersensitivity to the active substance or to one of the excipients of Ozurdex®, Kenacort® or injectable fluorescein
• Pregnant woman or likely to become pregnant or nursing
• Patient participating in another clinical trial
• Adult under a legal protection regime (guardianship, trusteeship, "sauvegarde de justice")

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Weber Michel, MD; (0)2 40 48 34 06 ext +33; michel.weber@chu-nantes.fr

Contact: Couret Chloé, MD; chloe.couret@chu-nantes.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02556424
• Other Study ID Numbers: RC15_0056
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Nantes University Hospital
• Study Sponsor: Nantes University Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nantes University Hospital
• Verification Date: January 2020